347P - The ENCHANTTM trial: an open label multicenter phase 2 window of opportunity study evaluating ganetespib (STA-9090) monotherapy in women with previo...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Drug Development
Breast Cancer, Metastatic
Presenter David Cameron
Authors D. Cameron1, M.S. Mano2, V. Vukovic3, F. Teofilovici4, R. Bradley4, A. Awada5
  • 1Oncology, Edinburgh Cancer CentreWestern General Hospital, GB-EH4 2XU - Edinburgh/UK
  • 2Medical Oncology, ICESP, Sao Paulo/BR
  • 3Clinical Development, Synta pharmaceuticals, lexington/US
  • 4Oncology, Synta pharmaceuticals, lexington/US
  • 5Medical Oncology, Institute Jules Bordet, 1000 - Brussels/BE



Hsp90 is a molecular chaperone required for proper folding and activation of many cancer-promoting proteins. Several Hsp90 clients are oncoproteins known to play a key role in the pathobiology of breast cancer, including HER2, p95-HER2, EGFR, ER, PI3K, AKT, and VEGFR. The inactivation of these oncoproteins by Hsp90 inhibition is a promising approach for breast cancer therapy. Ganetespib is an Hsp90 inhibitor which has shown anti-tumor activity in heavily pretreated patients with lung, breast, and other cancers. Ganetespib is well tolerated without severe liver or common ocular toxicities. In a phase 2 trial, 22 breast cancer patients who had received up to 3 prior lines of chemotherapy including trastuzumab were treated with ganetespib monotherapy. In patients with HER2+ disease, the objective response rate (ORR) was 15% (2/13) and the SD rate was 46% (6/13). Only 3 patients presented with TNBC; one of those patients achieved SD with substantial tumor shrinkage on treatment.


This is a single arm international open-label Phase 2 study in patients with HER2 amplified, or triple negative breast cancer. Patients must not have received any prior therapy in the metastatic setting. Prior adjuvant therapy is allowed. Primary endpoint: ORR. Main secondary endpoints include disease control rate, and progression free survival. Additionally, fresh biopsies and serum samples are collected from all patients for determination of predictors of response and mechanisms of resistance to treatment. Patients are treated with ganetespib 150 mg/m2 is given twice weekly of a 4-week cycle for up to 12 weeks. A total of 70 patients are planned for accrual. At the time of submission, the study is receiving IRB approvals in several centers.


All authors have declared no conflicts of interest.